Hookworms remain a major health burden in the developing world, with over one billion persons infected and hundreds of millions suffering from clinically relevant pathology. Substantial future reduction of hookworm disease will likely require the joining of conventional control strategies with novel approaches such as vaccines aimed at ameliorating the clinical sequelae caused by blood feeding adult parasites. Vaccine development will be most efficient if protective immune responses are identified and characterized in suitable animal models. Adult blood feeding hookworms residing in the host intestine secrete various proteins that are known to induce robust systemic immune responses. By contrast, mucosal immune responses in and around the site of attachment are not as well described. We hypothesize that adult hookworms residing in the host intestine induce specific mucosal immune responses in both the humoral and cellular compartments, and that these in turn play a role in acquired resistance to hookworm disease. We further hypothesize that mucosal vaccination may be employed to artificially induce resistance to hookworm infection and/or disease. Accordingly, the aim of this project will be to characterize mucosal immune responses in the hamster model of Ancylostoma ceylanicum hookworm infection to the antibody, cellular, and cytokine levels. A mucosal immunization protocol will be optimized using soluble hookworm extracts delivered by the oral route. Immunogenicity of mucosal immunization will be evaluated using enzyme-linked immunosorbent assay and immunoblot, and protective efficacy will be assessed using clinical measurements of anemia, growth, and worm burden. The optimized mucosal immunization protocol will then be used to evaluate the protective efficacy of adult hookworm antigens which have been previously identified and expressed as recombinant) proteins. These studies are expected to further our understanding of host-parasite immunological interaction and advance hookworm vaccine research through the development of novel immunization techniques.